ACUITY Gender and Outcomes

Gender Differences in Outcomes Following Percutaneous Coronary Intervention of Patients with Non-ST elevation Acute Coronary Syndrome A Substudy of the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial Ken Mori1, Alexandra J. Lansky1, Ricardo A. Costa1, Angel Cequier2, Charles V. Pollack, Jr.3, James Hoekstra4, Michel Bertrand5, Bernard Gersh6, Gregg W. Stone1 Cardiovascular Research Foundation Columbia University Medical Center 1Cardiovascular Research Foundation, New York, NY; 2Bellvitge University Hospital, Barcelona, Spain 3Duke University Medical Center, Durham, NC; 4Wake Forest University School of Medicine, Winston-Salem, NC; 5Hospital Cardiologique, Lambersart, France 6Mayo Clinic College of Medicine, Rochester, MN Background Women are at increased risk for vascular complications compared to men. (Leslie Cho, et al, JACC 2000;36: 381-6) Bivalirudin with provisional GPIIb/IIIa inhibitor is not inferior to heparin with planned GPIIb/IIIa inhibitor during contemporary PCI with regard to suppression of acute ischemic complications, and is associated with less bleeding. (A.Michael Lincoff, et al, JAMA 2003;289: 853-863) ACUITY Trial Design • Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,800) Angiography within 72h UFH or Enoxaparin + GP IIb/IIIa Medical management Moderatehigh risk ACS Aspirin in all Clopidogrel dosing and timing per local practice R* Bivalirudin + GP IIb/IIIa PCI Bivalirudin Alone CABG *Stratified by pre-angiography thienopyridine use or administration ACUITY Design. Stone GW et al. AHJ 2004;148:764–75 Major entry criteria ►Moderate-high risk unstable angina or NSTEMI Inclusion Criteria  Age ≥18 years  Chest pain ≥10’ within 24h  At least one of: New ST depression or Exclusion Criteria  No angiography within 72h  Acute STEMI or shock  Bleeding diathesis or major bleed transient ST elevation ≥1 mm Troponin I, T, or CKMB Documented CAD All other 4 TIMI risk criteria - Age ≥65 years - Aspirin within 7 days - ≥2 angina episodes w/i 24h within 2 weeks  Platelet count ≤100,000/mm3  INR >1.5 control  CrCl ≤30 ml/min  Abcx or ≥2 prior LMWH doses Prior UFH, LMWH (1 dose), eptifibatide and tirofiban were allowed  Allergy to drugs, contrast ACUITY Design. Stone GW et al. AHJ 2004;148:764–75 - ≥3 cardiac risk factors  Written informed consent ACUITY Primary Results (ITT) • Heparin* + IIb/IIIa vs. Bivalirudin + IIb/IIIa vs. Bivalirudin Alone Heparin+IIb/IIIa (N=4603) Bivalirudin+IIb/IIIa (N=4604) Bivalirudin alone (N=4612) 30 day events (%) PNI <0.001 PSup = 0.015 PNI = 0.011 PSup = 0.32 PNI <0.001 PSup <0.001 11.7% 11.8% 10.1% 7.3% 7.7% 7.8% 5.7% 5.3% 3.0% Net clinical outcome *Heparin=unfractionated or enoxaparin Composite ischemia Major bleeding (nonCABG) Non CABG Major bleeding definitions for ACUITY Intracranial bleeding Intraocular bleeding Access site hemorrhage requiring intervention ≥5 cm diameter hematoma Reduction in hemoglobin concentration of ≥4g/dL without an overt source of bleeding Reduction in hemoglobin concentration of ≥3 g/dL with an overt source of bleeding Re-operation for bleeding Use of any blood product transfusion ACUITY Major Bleeding Endpoints • Heparin* + IIb/IIIa vs. Bivalirudin + IIb/IIIa vs. Bivalirudin Alone Heparin+IIb/IIIa (N=4603) Bivalirudin+IIb/IIIa (N=4604) Bivalirudin alone (N=4612) PSup=0.31 PSup0.001 PSup=0.38 PSup<0.001 30 day events (%) 11.8% 11.1% 9.1% 5.7% 5.3% 3.0% All Major Bleeding (All, including CABG) *Heparin=unfractionated or enoxaparin Major Bleeding (Non-CABG related) Current Analysis Objective: The purpose of this analysis is to evaluate the outcome of women compared to men with acute coronary syndrome undergoing PCI in the ACUITY trial. Methods: Comparison of clinical presentation at baseline, angiographic characteristics and outcomes at 30 days in men vs. women with ACS who underwent PCI 13819 ACS patients (4157 female/ 9662 male) 7789 underwent PCI (2091 female/5698 male) All patients (including PCI, CABG and medication patients) Baseline Clinical Characteristics All patients N=13819 Age, years Diabetes, % Hypertension, % Current Smoker, % FEMALE N=4157 MALE N=9662 P value <0.0001 <0.0001 <0.0001 <0.0001 65.1 ±11.8 61.5 ±11.4 32.6 73.8 24.5 26.2 64.1 31.1 Previous MI, % Previous PCI, % Previous CABG, % Renal insufficiency*, % Previous use of Thienopyridine, % CKMB/Troponin elevation, % *Defined as creatinine clearance < 60 mL/min. 26.2 36.4 13.2 30.0 62.3 56.1 33.5 39.9 19.9 14.4 64.6 60.8 <0.0001 0.0001 <0.0001 <0.0001 0.009 <0.0001 Angiographic Characteristics All QCA Patients N=6921 Jeopardy Score Ejection Fraction, % TIMI Flow Grade, % - 0/1 -2 6.2 2.8 9.7 5.9 FEMALE N=2274 1.9±2.6 66.1±11.7 MALE N=4647 2.6±2.8 63.2±12.3 P value <0.0001 <0.0001 <0.0001 -3 Myocardial Blush Grade, % - 0/1 -2 -3 90.9 84.3 <0.0001 6.2 10.2 83.6 9.8 13.9 76.2 Angiographic Characteristics All QCA Patients N=6921 Lesions / pts # of diseased vessel, % FEMALE N=2274 3.4±2.7 MALE N=4647 4.4±3.0 P value <0.0001 - 0VD - 1VD - 2VD - 3VD Extent of disease, mm Lesion Location, % - LAD 14.7 23.4 27.7 34.1 36.0±28.2 67.6 6.6 16.0 28.2 49.1 41.8±30.8 78.1 <0.0001 <0.0001 0.67 <0.0001 <0.0001 <0.0001 - RCA - LCX 59.5 54.0 72.7 69.0 <0.0001 <0.0001 30-day Clinical events in all Patients (%) 15 p<0.0001 Female Male 13.1 10.4 10 P=0.06 7.9 7.0 P=0.28 p<0.0001 7.6 5 4.8 5.2 P=0.10 P=0.29 1.6 3.4 2.1 2.6 1.3 0 Net Clinical Composite Ischemia Events Death MI Ischemic Major revascularization bleeding PCI patients ACUITY Trial in PCI patients Unstable angina or non ST-segment elevation MI (n=7789) Prospect, randomized, multi-center trial ASA + clopidogrel (theinopyridine dosing and timing pre local practice) Angioplasty within 72 hours Bivalirudin UFH or Enoxaparin + GPI Women N=1110, Lesion=1447 Bivalirudin + GPI Men N=2554, Lesion=3466 30-day endpoints Composite ischemia (Death, MI and ischemic revascularization) Net clinical outcomes (Composite ischemia and Major bleeding) PCI Patients Characteristics FEMALE MALE P value Age, years Diabetes, % Hypertension, % Current Smoker, % 65.9 ±11.6 34.5 74.8 26.9 61.5 ±11.3 25.1 62.1 32.4 <0.0001 <0.0001 <0.0001 <0.0001 Previous MI, % Previous PCI, % Previous CABG, % Renal insufficiency*, % *Defined as creatinine clearance < 60 mL/min. 26.2 37.7 13.1 30.9 32.0 39.0 19.1 13.9 <0.0001 0.26 <0.0001 <0.0001 Angiographic Characteristics PCI QCA Patients N=3664 Lesions / pts FEMALE N=1110 3.9±2.4 MALE N=2554 4.5±2.7 P value <0.0001 # of diseased vessel, % - 1VD - 2VD - 3VD Extent of disease, mm 24.0 35.4 39.6 36.4±25.2 16.8 33.1 49.8 40.6±27.1 <0.0001 0.17 <0.0001 <0.0001 Lesion Location, % - LAD - RCA - LCX Jeopardy Score 78.2 72.4 63.1 2.4±2.3 81.5 77.1 73.7 2.7±2.3 0.0197 0.0027 <0.0001 0.0001 Ejection fraction, % 65.2±12.1 63.2±12.2 0.0002 Target vessel FEMALE Target Vessel, % MALE P value - LAD - RCA 36.5 35.9 33.9 33.5 0.08 0.11 - LCX - SVG 27.6 5.2 32.6 9.0 0.0006 <0.0001 - IMA 0.3 0.3 0.92 PCI lesion Characteristics FEMALE MALE P value TIMI flow, % - 0/1 -2 -3 10.7 7.7 81.6 13.1 10.3 76.6 0.0188 0.0051 0.0001 Myocardial blush grade, % - 0/1 -2 -3 13.0 15.3 71.8 16.6 15.8 67.6 0.0026 0.68 0.0074 PCI lesion Characteristics FEMALE Lesion Morphology, % Thrombus Eccentric Ulcerated Aneurysm Ectasia Calcium - Moderate - Severe ACC/AHA B2/C, % 19.9 3.5 55.2 21.9 3.5 60.7 0.13 0.99 0.0003 13.2 21.8 3.9 0.9 4.9 15.6 20.6 5.0 1.5 6.2 0.0349 0.33 0.09 0.09 0.09 MALE P value QCA method 5 mm Proxima l Edge In-Stent 5 mm Distal Edge Analysis Segment In-stent QCA results FEMALE Pre Procedure RVD, mm MLD , mm % DS MALE 2.8 ±0.6 0.7 ± 0.5 73.9 ± 15.8 P value <0.0001 0.57 0.06 2.7 ± 0.5 0.7 ± 0.5 72.9 ± 15.8 Lesion length, mm Post procedure In-segment MLD, mm %DS 14.8 ± 9.4 16.0 ± 10.3 <0.0001 2.3 ± 0.5 15.1 ± 10.2 2.3 ± 0.6 15.2 ± 10.7 <0.0001 0.84 Acute gain, mm In-stent MLD, mm %DS Acute gain, mm 1.5 ± 0.6 2.6 ± 0.5 16.6 ± 11.1 1.9 ± 0.5 1.6 ± 0.6 2.7 ± 0.5 17.4 ± 11.8 2.0 ± 0.6 <0.0001 <0.0001 0.08 0.0001 Post procedural morphology FEMALE TIMI flow, % MALE P value - 0/1 -2 -3 Myocardial blush grade, % - 0/1 1.3 1.0 97.8 1.8 1.4 2.3 96.3 2.5 0.65 0.002 0.008 0.17 -2 -3 Morphology Thrombus, % No reflow, % 9.1 89.1 0.4 0.2 11.4 86.1 1.0 0.1 0.028 0.009 0.044 0.27 Dissection, % Distal embolization, % 0.6 0.7 0.6 0.5 0.83 0.47 30-day clinical outcomes in PCI patients (%) p<0.0001 Female N=2091 17.3 15 Male N=5698 11.7 10 p=0.55 p<0.0001 10.5 9.1 8.7 P=0.25 6.7 6.0 p=0.54 3.2 3.5 5 p=0.71 1.0 1.1 4.2 0 Net Clinical Composite Outcomes Ischemia Death MI Ischemic Major revascularization bleeding Composite ischemia is defined as death, MI and ischemic revascularization. Net clinical outcome is defined as composite ischemia and major bleeding. Bleeding complications FEMALE Major bleeding, % Intracranial bleeding, % Access site bleeding, % Hematoma ≥5cm diameter, % Hb≥4g/dL fall without overt source , % Hb≥3g/dL fall with overt source , % Re-operation for bleeding , % Blood product transfusion , % MALE 4.2 0.0 0.3 1.7 0.7 1.6 0.1 1.7 P value <0.0001 0.80 <0.0001 <0.0001 <0.0001 <0.0001 0.75 <0.0001 10.7 0.0 1.3 3.8 1.9 4.2 0.1 6.0 Non-CABG Bleeding in Women undergoing PCI • Heparin + IIb/IIIa vs. Bivalirudin Alone Heparin+IIb/IIIa (N=701) Bivalirudin alone (N=700) P< 0.001 P=0.002 P<0.001 P=0.07 30 day events (%) 11.8% 11.8% 6.3% 4.0% 1.3% 6.3% 6.3% 4.1% Major Bleeding TIMI Major TIMI Minor Transfusions Conclusions Women with ACS undergoing primary PCI showed similar 30-day composite ischemic complications compared to men, despite being older, and having more co-morbidites. Women had statistically significant increase in major bleeding complications compared to men. Bivalirudin alone as compared to Heparin + IIb/IIIa provided significant bleeding advantage in women undergoing PCI. Women with ACS were older, with more diabetes, hypertension, chronic renal insufficiency and low ejection fraction, but more normal epicardial flow (TIMI 3) and fewer lesions per patient compared to men.